DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Applicant’s Response to Election/Restriction Filed, Amendment, and Arguments/Remarks, filed 13 April 2026, have been entered. No claims were cancelled and no new claims were added. Claims 1-3, 6, 8, 14-21, 57, 60, 63, 65, 71-76, 83-85, 88, and 94-102 are currently pending. Claims 1, 57, and 83 are independent claims. Applicant’s election without traverse of the invention of Group I, drawn to a method for improving growth of cells cultured in a liquid media and a method for improving the growth of mammalian cells engineered to produce a first recombinant protein, is acknowledged.
Additionally, applicant’s election of the following species:
Enzymes that hydrolyze at least one nucleoside triphosphate addition method: a. exogenously added to media, and
Recombinant cell products: a. enzyme;
is acknowledged. While Applicant has not indicated whether these elections of species have been made with or without traverse, Applicant has not provided any arguments traversing the election of species requirement(s). Therefore, the election of species 1)a. exogenously added to media and 2)a. enzyme is considered to have been made without traverse.
Claims 57, 60, 63, 65, and 71-76 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Claims 16, 96, and 99-101 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim.
Claims 1-3, 6, 8, 14-15, 17-21, 83-85, 88, 94-95, 97-98, and 102 are currently pending in the application and under examination to which the following grounds of rejection are applicable. An action on the merits follows.
Priority
The present application is a 35 U.S.C. 371 national stage filing of International Application No. PCT/US2022/035530, filed 29 June 2022, which claims priority to U.S. Provisional Application Nos. 63/335,419, filed 27 April 2022, 63/330,693, filed 13 April 2022, and 63/216,193, filed 29 June 2021.
Thus, the earliest possible priority for the instant application is 29 June 2021.
Specification
The use of the term “Synergy HTX” in [0149], which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore, the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Note that the specification has not been inspected sufficiently to identify all recitations of trade names and/or marks used in commerce. It is Applicant’s responsibility to ensure complete compliance.
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-3, 6, 8, 14-15, 17-21, 83-85, 88, 94-95, 97-98, and 102 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention. Dependent claims 2-3, 6, 8, 14-15, 17-21, 84-85, 88, 94-95, 97-98, and 102 are included in this rejection due to their dependence on independent claims 1 or 83.
The term “improved” in claims 1 and 83 in lines 3 and 4, respectively, is a relative term which renders the claim indefinite. The term “improved” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
Although the claims 1 and 83 each recite “compared to cells cultured in media that does not comprise one or more enzymes that hydrolyzes at least one nucleoside triphosphate in lines 3-5 and 4-6, respectively, the comparison does not provide for what changes relative to the comparison/control condition would constitute “improved growth”.
Although the term “improved” is recited and further limited in claims 2 and 84 (line 1 of each), the dependent claims 2 and 84 merely serve to further limit the scope of the “improved growth” recited in independent claims 1 and 83. Therefore, although claims 2 and 84 provide bounds to the further limited scope of “improved growth”, they merely indicate embodiments within the scope of “improved growth” and do not establish the metes and bounds of the phrase as used in independent claims 1 and 83. As such, the metes and bounds of the claims cannot be determined.
The specification defines “improved growth” as follows: “[0029] The phrase 'improving growth of cells cultured in a liquid media" or "improved growth" refers to improving the yield or viability of any cell cultured or fermented in a nutrient-rich liquid medium over a given period of time.” However, because the specification defines “improved growth” by saying it is “improved yield or viability”, the specification has not provided clarity regarding the metes and bounds of what would constitute “improved”.
Claim 17, which depended on claim 14, and claim 97, which depends on claim 94, are indefinite in their recitation of “the primary cell”. There is insufficient antecedent basis in the claims. The parent claims recite “primary cells”.
As such, the metes and bounds of the claims cannot be determined.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 1-3, 6, 14, and 17-20 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Zanin et al. [2012, PLoS ONE, 7(2), e31205, 1-10].
Regarding claim 1, Zanin discloses a method for improving growth of mammalian cells (i.e., primary mouse macrophages) cultured in a liquid media comprising culturing the cells in a media comprising one or more enzymes that hydrolyze at least one nucleoside triphosphate (i.e., potato apyrase), wherein the cells exhibit improved growth (i.e., reduced cell death) compared to cells cultured in media that does not comprise the potato apyrase [abstract, pp 2 col 2 ¶ 2, pp 3 col 2 ¶ 2, pp 5 col 2 ¶ 2, Figure 6].
Regarding claim 2, as discussed above, Zanin discloses wherein the improved growth is decreased cell death/ higher post-culture viability [pp 3 col 2 ¶ 2, pp 5 col 2 ¶ 2, Figure 6].
Regarding claims 3 and 6, Zanin discloses wherein the enzyme is potato apyrase, which scavenges/hydrolyzes ATP [pp 3 col 2 ¶ 2, pp 5 col 2 ¶ 2, pp 9 col 2 ref 34, Figure 6].
Regarding claims 14, 17, and 18, as discussed above, Zanin discloses wherein the cells are primary mouse macrophages, and so teaches that the cells are primary leukocytes [abstract, pp 2 col 2 ¶ 2].
Regarding claims 19-20, Zanin teaches wherein the potato apyrase is exogenously added to the media, as elected [pp 3 col 2 ¶ 2, pp 5 col 2 ¶ 2, Figure 6]. Zanin does not teach that the potato apyrase is recombinantly expressed by the primary mouse macrophages, and so the cells are presumed to lack recombinant potato apyrase activity absent evidence to the contrary. Additionally, potato apyrase is endogenous to potato plants, and therefore is not naturally produced by the primary mouse macrophages.
Accordingly, by teaching all of the limitations of instant claims 1-3, 6, 14, and 17-20 as written, Zanin anticipates the instant invention as claimed.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 1-3, 6, 8, 14-15, 17-21, 83-85, 88, 94-95, 97-98, and 102 are rejected under 35 U.S.C. 103 as being unpatentable over Zanin et al. [2012, PLoS ONE, 7(2), e31205, 1-10]; in view of Kan et al. [2011, International Journal of Molecular Medicine, 27, 173-180]; and NCBI [2013, Apyrase precursor [Solanum tuberosum], retrieved on 02 July 2026 from: www.ncbi.nlm.nih.gov/protein/NP_001275348.1?report=genbank&log$=protalign&blast_rank=1&RID=4DBWFAZM016, sequence updated 20 December 2013].
Regarding independent claim 1, Zanin discloses a method for improving growth of mammalian cells (i.e., primary mouse macrophages) cultured in a liquid media comprising culturing the cells in a media comprising one or more enzymes that hydrolyze at least one nucleoside triphosphate (i.e., potato apyrase), wherein the cells exhibit improved growth (i.e., reduced cell death) compared to cells cultured in media that does not comprise the potato apyrase [abstract, pp 2 col 2 ¶ 2, pp 3 col 2 ¶ 2, pp 5 col 2 ¶ 2, Figure 6].
Regarding independent claim 83, Zanin also teaches wherein the potato apyrase is exogenously added to the media, as elected [pp 3 col 2 ¶ 2, pp 5 col 2 ¶ 2, Figure 6].
Zanin does not teach wherein the mammalian cells are engineered to produce a first recombinant protein. Note that although “for improving the growth of mammalian cells engineered to produce a first recombinant protein” in lines 1-2 constitutes an intended use for the method, recitation of “culturing the mammalian cells” in line 2 requires that the cells which are cultured be the mammalian cells engineered to produce a first recombinant protein.
Kan teaches primary human macrophages genetically engineered to produce a recombinant protein as a treatment for cancer, wherein the recombinant protein is the enzyme cytochrome P450 2B6 (CYP2B6) and human P450 reductase (P450R), which process the prodrug CPA into its active form [abstract, pp 174 col 2 ¶ 2]. Kan teaches that the genetically modified macrophages showed increased cytotoxicity against various tumor cell lines compared to untransduced macrophages [abstract]. Kan also teaches that their results suggest a benefit of developing a genetically engineered macrophage for the treatment of cancer, wherein the treatment strategy involves patients undergoing apheresis to collect autologous monocytes, maturation to macrophages, ‘arming’ of the macrophages via transduction with the Ad-PR vector and re-administration directly into the peritoneal cavity followed by intraperitoneal infusion of CPA [pp 179 col 1 ¶ 2].
Therefore, an ordinarily skilled artisan would have been motivated to genetically modify primary mammalian macrophages to express a recombinant enzyme, such as cytochrome P450 2B6 and P450 reductase, and in so doing would be motivated to culture the modified macrophages under conditions which provide optimized/improved growth of the macrophages in vitro/ex vivo.
Regarding claims 2 and 84, as discussed above, Zanin discloses wherein the improved growth is decreased cell death/ higher post-culture viability [pp 3 col 2 ¶ 2, pp 5 col 2 ¶ 2, Figure 6].
Regarding claims 3, 6, 85, and 88, Zanin discloses wherein the enzyme is potato apyrase, which scavenges/hydrolyzes ATP [pp 3 col 2 ¶ 2, pp 5 col 2 ¶ 2, pp 9 col 2 ref 34, Figure 6].
Regarding claims 14, 17, 18, 94, 97, and 98 as discussed above, Zanin discloses wherein the cells are primary mouse macrophages, and so teaches that the cells are primary leukocytes [abstract, pp 2 col 2 ¶ 2].
Regarding claims 8, 15, and 95, as discussed above, Kan teaches primary human macrophages genetically engineered to produce a recombinant protein as a treatment for cancer, wherein the recombinant protein is the enzyme cytochrome P450 2B6 (CYP2B6) and human P450 reductase (P450R), which process the prodrug CPA into its active form [abstract, pp 174 col 2 ¶ 2].
Regarding claims 19-20, Zanin teaches wherein the potato apyrase is exogenously added to the media, as elected [pp 3 col 2 ¶ 2, pp 5 col 2 ¶ 2, Figure 6]. Zanin does not teach that the potato apyrase is recombinantly expressed by the primary mouse macrophages, and so the cells are presumed to lack recombinant potato apyrase activity absent evidence to the contrary. Additionally, potato apyrase is endogenous to potato plants, and therefore is not naturally produced by the primary mouse macrophages.
Regarding claims 21 and 102, as discussed above, Zanin teaches to add potato apyrase to the culture media of primary mammalian macrophages to reduce cell death.
Zanin does not teach wherein the potato apyrase has an amino acid sequence at least 60% identical to the amino acid sequence of SEQ ID NOs: 1, 2, 3, or 4 as recited in claims 21 and 102.
However, NCBI teaches that the amino acid sequence of a natural potato apyrase sequence from Solanum tuberosum has 99% identity to the full-length sequence of instant SEQ ID NO: 3 and 99% identity to the full-length sequence of instant SEQ ID NO: 4, as depicted in the following alignments.
NCBI apyrase precursor [Solanum tuberosum] vs instant SEQ ID NO: 3:
PNG
media_image1.png
625
670
media_image1.png
Greyscale
NCBI apyrase precursor [Solanum tuberosum] vs instant SEQ ID NO: 4:
PNG
media_image2.png
626
678
media_image2.png
Greyscale
Therefore, the potato apyrase taught by Zanin either itself has an amino acid sequence at least about 60% identical to the amino acid sequence of instant SEQ ID NO: 4, or an ordinarily skilled artisan at the time of filing would have been motivated to use a potato apyrase which has an amino acid sequence at least about 60% identical to the amino acid sequence of instant SEQ ID NOs: 3 or 4 in view of the teachings of NCBI of a naturally-occurring potato apyrase which is 99% identical to the amino acid sequences of instant SEQ ID NO: 3 and 4.
Given the motivation taught by Kan to genetically modify primary mammalian macrophages to express a recombinant enzyme, such as cytochrome P450 2B6 and P450 reductase, and in so doing would be motivated to culture the modified macrophages under conditions which provide optimized/improved growth of the macrophages in vitro/ex vivo; and the teachings of NCBI of a naturally occurring potato apyrase amino acid sequence which is 99% identical to the amino acid sequences of instant SEQ ID NOs: 3 and 4; it would have been prima facie obvious to an ordinarily skilled artisan at the time of filing the instant application to modify the method of Zanin to utilize a mammalian cell engineered to produce a recombinant enzyme and to use a potato apyrase with an amino acid sequence at least about 60% identical to the amino acid sequence of instant SEQ ID NO: 3 or 4 with a reasonable expectation of success.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Dr. KATIE L PENNINGTON whose telephone number is (703)756-4622. The examiner can normally be reached M-Th 8:30 am - 5:30 pm, Friday 8:30 am - 12:30 pm CT.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Maria G. Leavitt can be reached on (571) 272-1085. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
DR. KATIE L. PENNINGTON
Examiner
Art Unit 1634
/KATIE L PENNINGTON/Examiner, Art Unit 1634
/MARIA G LEAVITT/Supervisory Patent Examiner, Art Unit 1634
Prosecution Insights